Phenotypes Associated with This Genotype

Genotype
MGI:3036452

• Allelic Composition: Crhr1^tm1Klee/Crhr1^tm1Klee; Crhr2^tm1Klee/Crhr2^tm1Klee
• Genetic Background: involves: 129S4/SvJae * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

abnormal anxiety-related response ( J:77641 )

• double homozygous mutant mice showed a sexually dichotomous anxiety-like behavior on the elevated plus maze: female double mutant mice displayed anxiolytic-like behavior, whereas male double mutant mice showed significantly increased anxiety-like behavior relative to females

• no significant differences were observed in center visits between female and male double mutant mice in the open-field test; however, female double mutant mice produced significantly fewer fecal boli, suggesting an anxiolytic-like behavior

• notably, the dam's genotype affects the anxiety-like behavior of double mutant males: a pup born to a heterozygous or homozygous mutant dam exhibits significantly increased anxiety-like behavior, regardless of that pup's genotype

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:77641 )

N • histology of the pituitary gland showed no anatomic abnormalities

decreased adrenal gland zona fasciculata size ( J:77641 )

• histologic analysis revealed hypoplasia of the zona fasciculata (corticosterone-producing region) of the adrenal cortex

adrenal gland atrophy ( J:77641 )

• similar to Crhr1^tm1Klee mutant mice, double mutant mice displayed atrophy of the adrenal gland due to agenesis of the adrenal cortex (hypoplasia of the zona fasciculata region)

homeostasis/metabolism

abnormal hormone level ( J:77641 )

• double homozygous mutant mice showed significantly lower basal levels of corticosterone compared to Crhr1^tm1Klee single mutant mice; in contrast, basal levels of POMC1 (ACTH) did not differ between control, Crhr1^tm1Klee single-, Crhr2^tm1Klee single-, and double mutant mice

• double homozygous mutant mice displayed a minimal HPA axis response to physical-restraint stress, with significantly lower POMC1 (ACTH) and corticosterone levels compared to Crhr1^tm1Klee single mutant mice

• CRH mRNA levels were increased in Crhr1^tm1Klee single- and double-mutant mice, and urocortin-3 and arginine vasopressin mRNA levels were increased in Crhr2^tm1Klee single- and double-mutant mice